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- Bondeson, Marie-Louise, et al.
(författare)
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Presence of an IDS-related locus (IDS2) in Xq28 complicates the mutational analysis of Hunter syndrome
- 1995
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Ingår i: European Journal of Human Genetics. - 1018-4813 .- 1476-5438. ; 3:4, s. 219-227
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Tidskriftsartikel (refereegranskat)abstract
- A deficiency of the enzyme iduronate-2-sulfatase (IDS) is the cause of Hunter syndrome (mucopolysaccharidosis type II). Here, we report a study of the human IDS locus at Xq28. An unexpected finding was an IDS-related region (IDS2) which is located on the telomeric side of the IDS gene within 80 kb. We have identified sequences in this locus that are homologous to exons 2 and 3 as well as sequences homologous to introns 2, 3 and 7 of the IDS gene. The exon 3 sequences in the IDS gene and in the IDS2 locus showed 100% identity. The overall identities of the other identified regions were 96%. A locus for DXS466 was also found to be located close to IDS2. The existence of the IDS2 locus complicates the diagnosis of mutations in genomic DNA from patients with Hunter syndrome. However, information about the IDS2 locus makes it possible to analyze the IDS gene and the IDS2 locus separately after PCR amplification.
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| 8. |
- Pigg, Maritta, et al.
(författare)
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Strong founder effect for a transglutaminase 1 gene mutation in lamellar ichthyosis and congenital ichthyosiform erythroderma from Norway
- 1998
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Ingår i: European Journal of Human Genetics. - 1018-4813 .- 1476-5438. ; 6:6, s. 589-96
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Tidskriftsartikel (refereegranskat)abstract
- Autosomal recessive congenital ichthyosis (ARCI) is a clinically heterogeneous disorder of keratinisation. It was recently shown that mutations in the transglutaminase 1 (TGM1) gene may be associated with the clinical subtypes lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (CIE). Thirty-six Norwegian families with LI and seven with non-bullous CIE were studied with microsatellite markers linked to the TGMI gene. One common haplotype for two markers was found on 74% of disease associated chromosomes. Three individuals homozygous for the common haplotype, two affected by LI and one affected by CIE, were analysed for mutations in the TGM1 gene. All three patients were found homozygous for a single A to G transition located in the canonical splice acceptor site of intron 5. Probands from the remaining 40 families with LI and CIE were screened for this mutation and the A to G transition was found on 61 out of 72 alleles associated with LI and on 9 out of 15 alleles associated with CIE. These findings suggest a single founder mutation for the majority of patients with LI and CIE in Norway. The 2526A-->G mutation results in the insertion of a guanosine at position 877 (876insG) in the mature cDNA and the frame shift creates a premature termination at codon 293. The mutation was previously observed in one family with a resulting cDNA that included the entire intron 5. These results suggest that the mutation can result in variant transcripts in different individuals.
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- Tentler, D., et al.
(författare)
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Deletion including the oligophrenin-1 gene associated with enlarged cerebral ventricles, cerebellar hypoplasia, seizures and ataxia
- 1999
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Ingår i: European Journal of Human Genetics. - 1018-4813 .- 1476-5438. ; 7:5, s. 541-8
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Tidskriftsartikel (refereegranskat)abstract
- Non-specific X-linked mental retardation is a heterogeneous group of disorders with an incidence of approximately 1 in 500 males. A recently identified gene in Xq12, encoding a Rho-GTPase-activating protein, was found to be mutated in individuals with mental retardation. We describe here two sisters with a 46,XY karyotype and a microdeletion of the oligophrenin-1 gene and 1.1 Mb of flanking DNA. We have characterised the molecular interval defining this microdeletion syndrome with the fibre-FISH technique. A visual physical map of 1.2 Mb was constructed which spans the oligophrenin-1 gene and the androgen receptor gene. The analysis of the patients revealed a deletion which extended from the 5' end of the AR gene to a region approximately 80 kb proximal to the EPLG2 gene. The clinical manifestations of the two sisters include psychomotor retardation, seizures, ataxia, hypotonia and complete androgen insensitivity. Cranial MRI scans show enlargement of the cerebral ventricles and cerebellar hypoplasia. Our findings give further support for the involvement of the oligophrenin-1 gene in specific morphological abnormalities of the brain which is of importance in the investigation of male patients presenting with mental retardation. In combination with our results from physical mapping we suggest that a region around the oligophrenin-1 locus is relatively bereft of vital genes.
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